Chang Chien Yi-Che, Madarász Kristóf, Csoma Szilvia Lilla, Mótyán János András, Huang Hsuan-Ying, Méhes Gábor, Mokánszki Attila
Department of Pathology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary.
Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary.
Cancers (Basel). 2023 Jan 31;15(3):898. doi: 10.3390/cancers15030898.
( corepressor)-rearranged sarcomas (BRSs) are a heterogeneous group of sarcomas previously classified as part of the group of "atypical Ewing" or "Ewing-like" sarcomas, without the prototypical gene translocation. Due to their similar morphology and histopathological features, diagnosis is challenging. The most common genetic aberrations are fusion and internal tandem duplication (ITD). Recently, various new fusion partners of have been documented, such as , , , and , further increasing the complexity of such tumor entities, although the molecular pathogenetic mechanism remains to be elucidated. Here, we present an index case of intrathoracic BRS that carried a novel (calmegin) gene fusion, exhibited by a 52-year-old female diagnosed initially by immunohistochemistry due to the positivity of a BCOR stain; the fusion was identified by next-generation sequencing and was confirmed by Sanger sequencing. In silico protein analysis was performed to demonstrate the 3D structure of the chimera protein. The physicochemical properties of the fusion protein sequence were calculated using the ProtParam web-server tool. Our finding further broadens the fusion partner gene spectrum of BRS. Due to the heterogeneity, molecular ancillary tests serve as powerful tools to discover these unusual variants, and an in silico analysis of the fusion protein offers an appropriate approach toward understanding the exact pathogenesis of such a rare variant.
(共抑制因子)重排肉瘤(BRSs)是一组异质性肉瘤,以前被归类为“非典型尤因”或“尤因样”肉瘤组的一部分,没有典型的基因易位。由于它们相似的形态和组织病理学特征,诊断具有挑战性。最常见的基因畸变是 融合和内部串联重复(ITD)。最近,已经记录了各种新的 融合伙伴,如 、 、 和 ,进一步增加了此类肿瘤实体的复杂性,尽管分子发病机制仍有待阐明。在这里,我们报告了一例胸腔内BRS的索引病例,该病例携带一种新的 (钙调蛋白)基因融合,由一名52岁女性表现出来,该女性最初因BCOR染色阳性通过免疫组织化学诊断;通过下一代测序鉴定融合,并通过桑格测序确认。进行了计算机蛋白质分析以展示嵌合蛋白的三维结构。使用ProtParam网络服务器工具计算融合蛋白序列的物理化学性质。我们的发现进一步拓宽了BRS的融合伙伴基因谱。由于其异质性,分子辅助检测是发现这些不寻常变异的有力工具,对融合蛋白的计算机分析为理解这种罕见变异的确切发病机制提供了一种合适的方法。